Following traumatic spinal cord injury (SCI), activated glia and inflammatory leukocytes contribute to both neurodegeneration and repair. The mechanisms that control these divergent functions are poorly understood. Toll-like receptors (TLRs) are a highly conserved family of receptors involved in pathogen recognition and host defense. However, recently it was shown that TLRs are expressed on a range of neuronal and non-neuronal cells (e.g., glia, stem/progenitor cells and leukocytes), and that nonpathogenic molecules released from sites of tissue injury, i.e., danger-associated molecular patterns (DAMPs), can activate cells via TLRs. This review will discuss how DAMPs acting at various TLRs may influence injury and repair processes of relevance to SCI, i.e., neurotoxicity, demyelination, growth cone collapse and stem/progenitor cell turnover.